Cholesterol Complexes of Redox-Active Nanoparticles Affect Redox Balance and Viability of Fibrosarcoma and Metastatic Bladder Cancer Cells

Abstract Ascorbic acid (AA) is well-known for its concentration-dependent redox activity with anticancer effects at pharmacological (high) concentrations. However, its therapeutic efficacy varies significantly across cancer types highlighting the need for novel approaches. In this study, the ability of CeO 2-x and GdYVO 4 :Eu 3+ NPs to provide redox imbalance and cell dysfunction as a result of enhanced ROS (reactive oxygen species) generation triggered by AA addition was revealed for fibrosarcoma (L929) and metastatic bladder cancer (T24T) cell lines. The observed potentiation of AA anticancer activity in combination with redox-active NPs is further enhanced in cholesterol-based supramolecular complexes (SMCs) incorporating NPs and menadione (vitamin K3), due to the synergistic action of their components. Comparison of several indicators of redox state of cancer cells (GSH/GSSG ratio, mitochondrial membrane potential, ATP, 8-isoprostane, and caspase-3 levels) revealed a higher antitumor efficacy of CeO 2-x NPs and CeO 2-x -based SMCs compared to GdYVO 4 :Eu 3+ NPs that can be ascribed to their superior redox cycling capability and higher efficiency in ROS generation in combination with pharmacological ascorbate.